HISTAMINE AND THE REVERSAL OF CHLORPROMAZINE-INDUCED DEPRESSION

¹ Department of Pharmacology, Sterling-Winthrop Research Institute, Rensselaer, New York

The ability of histamine and other substances to counteract chlorpromazine-induced depression was observed as a reversal or prevention of the prostration and behavioral deficit following chlorpromazine injections. Histamine, reserpine and several antihistamines counteracted the depression while -methyl-meta-tyrosine was ineffective. Pregnant mice and mice pretreated with the diamine oxidase inhibitor aminoguanidine, were resistant to chlorpromazine-induced depression. The data were interpreted as suggesting: 1. Depression induced by chlorpromazine may reflect in part some specific central antihistaminic activity not shared by the nonantipsychotic antihistamines. 2. Histamine has a role in the CNS, some parameters of which may be mediated through systems subserving overt manifestations of consciousness, awareness, arousal thresholds or motor co-ordination.